Background: Cancer is a well-established risk factor for the development of pulmonary embolism (PE), especially the. gastrointestinal (GI) cancers. While multiple studies have reported the burden of PE in cancer patients, recent data comparing in-hospital outcomes among different types of cancer patients are lacking. This study aimed to investigate the clinical and healthcare utilization outcomes of hospitalized patients with acute PE in the context of gastrointestinal (GI) cancers. Methods: A cross-sectional study was conducted using data from the National Inpatient Sample (2016-2020). International Statistical Classification of Diseases (ICD-10) codes were employed to identify hospitalized patients admitted with primary diagnosis acute PE. Data regarding GI cancer diagnosis along with demographic information, baseline clinical characteristics, and outcome variables, including mortality, hospital length of stay, total hospital charges, complications and risk factors were collected and analyzed. Statistical analysis was performed using the survey procedures function in STATA v.17, with statistical significance defined by the t-test at a significance level of p < 0.05. Results: Among the 181,060 patients admitted with primary diagnosis of acute pulmonary embolism, 550 (0.3%) had underlying gastric cancer, 1,790 (0.98%) had pancreatic cancer, 875 (0.48%) had hepatobiliary cancer, and 2,600 (1.61%) had small intestine and colorectal cancer. Mortality was found to be significantly higher in all types of GI cancer, with gastric cancer demonstrating the highest mortality rate (10%). After adjusting for age, sex, race, payment category, comorbidities, and risk factors of PE, gastric cancer (OR 2.6; 95% CI: 1.1-6.2) and pancreatic cancer (OR 2.2; 95% CI: 1.4-3.4) were found as independent risk factors for mortality. There was no significant difference in mean length of hospital stays and mean total hospital charges in patients with or without cancer. Similarly, no significant differences were observed in complications such as requirement for mechanical ventilation, arrhythmia, cardiac arrest, need for vasopressor and thrombolysis. Conclusions: In-hospital mortality in patients with acute pulmonary embolism is significantly higher in all types of GI cancer, however; there is no significant differences in hospital length of stay and total hospital charges in patients with or without cancer.